Skip to main content
Log in

Lack of epinine formation in adrenal medulla and brain of rats during cold exposure and inhibition of dopamine β-hydroxylase

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

Cold exposure of rats for 4 h and simultaneous inhibition of dopamine β-hydroxylase by FLA-63 (25 mg/kg) led to a reduction of the catecholamine content of the adrenal medulla by 46% and of the brain by 68%. Additional injections of 5 mg/kg FLA-63 4 and 9 h after beginning of the experiments, respectively, kept the catecholamine content on this low level (brain) or decreased in further (adrenal medulla). Administration of 5 mg/kg (-)DOPA together with the mono-amine oxidase inhibitor pargyline (50 mg/kg) 24 h after the first injection of FLA-63 stimulated the resynthesis. It amounted for the adrenal medulla to 20 μg/kg body weight/8 h and for the brain to 45 ng/g tissue wet weight/8 h. Paper chromatographic analyses of the extracts of adrenal medulla and brain, respectively, performed at each time of the different injections, clearly identified adrenaline, noradrenaline and dopamine (in traces) in the adrenal medulla as well as noradrenaline and dopamine in the brain; epinine on the contrary could not be demonstrated, not even in traces. Since at least 25 ng of epinine can be detected with certainty by our method, it can be concluded that epinine is not formed in amounts greater than 75 ng/pair adrenal glands or 37.5 ng/brain. The present results support the view that the main pathway of adrenaline biosynthesis in the suprarenal medulla and the brain proceeds via noradrenaline and not via epinine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Axelrod, J.: Purification and properties of phenylethanolamine-N-methyl transferase. J. biol. Chem. 237, 1657–1660 (1962)

    Google Scholar 

  • Blaschko, H.: The specific action of l-Dopa decarboxylase. J. Physiol. (Lond.) 96, 50P-51P (1939)

    Google Scholar 

  • Ellman, G. L.: Determination of epinephrine and related compounds on paper chromatograms. Nature (Lond.) 181, 768–769 (1958)

    Google Scholar 

  • Florvall, L., Corrodi, H.: Dopamine β-hydroxylase inhibitors. Acta pharm. suecica 7, 7–22 (1970)

    Google Scholar 

  • Hofman, A. R., Ciaranello, R. D., Axelrod, J.: Substrate and inhibitor kinetics of bovine phenylethanolamine-N-methyltransferase. Biochem. Pharmacol. 24, 544–546 (1975)

    Google Scholar 

  • Holtz, P.: Dopadecarboxylase. Naturwissenschaften. 27, 724–725 (1939)

    Google Scholar 

  • Hsu, L. L., Mandell, J. M.: Multiple N-methyltransferases for aromatic alkylamines in brain. Life Sci. 13, 847–858 (1973)

    Google Scholar 

  • Kirshner, N.: Uptake of catecholamines by a particulate fraction of the adrenal medulla. J. biol. Chem. 237, 2311–2317 (1962)

    Google Scholar 

  • Kirshner, N., Goodall, C. Mc.: The formation of adrenaline from noradrenaline. Biochim. biophys. Acta (Amst.) 24, 658–659 (1957)

    Google Scholar 

  • Korevaar, W. C., Geyer, M. A., Knap, S., Hsu, L. L., Mandell, A. J.: Regional distribution of 5-methyltetrahydrofolic acid in brain. Nature New Biol. 245, 244–245 (1973)

    Google Scholar 

  • Laduron, P.: N-Methylation of dopamine to epinine in adrenal medulla: a new model for the biosynthesis of adrenaline. Arch. int. Pharmacodyn. 195, 197–208 (1972)

    Google Scholar 

  • Laduron, P.: N-Methylation of dopamine to epinine in brain tissue using N-methyltetrahydrofolic acid as the methyl donor. Nature New Biol. 238, 212–213 (1972a)

    Google Scholar 

  • Laduron, P., Belpaire, F.: Tissue fractionation and catecholamines. II. Intracellular distribution patterns of tyrosine hydroxylase, dopa decarboxylase, dopamine β-hydroxylase, phenylethanolamine-N-methyltransferase and monoamine oxidase in adrenal medulla. Biochem. Pharmacol. 17, 1127–1140 (1968)

    Google Scholar 

  • Laduron, P., Gommeren, W. R., Leysen, J. E.: N-Methylation of biogenic amines. I. Characterization and properties of a N-methyltransferase in rat brain using 5-methyltetrahydrofolic acid as the methyl donor. Biochem. Pharmacol. 23, 1599–1608 (1974a)

    Google Scholar 

  • Laduron, P., Van Gompel, P., Leysen, J., Claeys, M.: In vivo formation of epinine in adrenal medulla. Naunyn-Schmiedeberg's Arch. Pharmacol. 286, 227–238 (1974)

    Google Scholar 

  • Meller, E., Rosengarten, H., Fiedhoff, A. J.: 5-Methyltetrahydrofolic acid is not a methyl donor for biogenic amines: enzymatic formation of formaldehyde. Science 187, 171–173 (1975)

    Google Scholar 

  • Palmer, J. F.: The use of β-thiopropionic acid for the analysis of mixtures of adrenaline and noradrenaline in plasma by the fluorometric trihydroxyindole method. West Indian med. J. 13, 38–53 (1964)

    Google Scholar 

  • Pendleton, R. G., Gessner, G.: Evidence that dopamine is not a substrate for adrenal phenylethanolamine-N-methyltransferase. Molec. Pharmacol. 11, 232–235 (1975)

    Google Scholar 

  • Schümann, H. J.: Die Wirkung von Insulin und Reserpin auf den Adrenalin- und ATP-Gehalt der chromaffinen Granula des Nebennierenmarks. Naunyn-Schmiedebergs Arch. Path. exp. Pharmak. 233, 237–249 (1958)

    Google Scholar 

  • Schümann, H. J., Grobecker, H.: Über die Wirkung von α-Methyldopa auf den Brenzcatechinamingehalt von Meerschweinchenorganen. Naunyn-Schmiedebergs Arch. Path. exp. Pharmak. 251, 48–61 (1965)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schümann, H.J., Brodde, O.E. Lack of epinine formation in adrenal medulla and brain of rats during cold exposure and inhibition of dopamine β-hydroxylase. Naunyn-Schmiedeberg's Arch. Pharmacol. 293, 139–144 (1976). https://doi.org/10.1007/BF00499218

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00499218

Key words

Navigation